P653: OUTCOMES FOLLOWING TREATMENT WITH A COVALENT BTK AND BCL2 INHIBITOR AMONG PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (CLL)/SMALL LYMPHOCYTIC LYMPHOMA (SLL): A REAL-WORLD STUDY OF A LARGE U.S. DATABASE
Authors: T. A. Eyre, L. Hess, T. Sugihara, R. A. Walgren, P. B. Abada, H. Konig, J. Pagel, L. E. Roeker, A. Mato
Journal: HemaSphere (2022)

Background: Covalent Bruton tyrosine kinase inhibitors (cBTKi) and B-cell lymphoma 2 inhibitors (BCL2i) have improved the outcomes for patients with CLL/SLL. Although these agents are highly effective, they are not curative, and over time patients will require additional therapy. Real-world data of patient outcomes post cBTKi and BCL2i exposure in CLL/SLL are limited to small retrospective studies, and the optimal treatment in this setting is unknown. Aims: This study was designed to address this data gap by evaluating the characteristics and clinical outcomes about patients with CLL/SLL after treatment with both cBTKi and BCL2i. Methods: Eligible patients were adult patients in the Flatiron Health Electronic Health Record (EHR)-derived de-identified database diagnosed with CLL/SLL between December 2011 and October[LMH1] 2020. Follow-up data were available through October 2021 at the time of analysis. Patients were required to have at least one record of receiving both a cBTKi and a BCL2i. Time-to-event analyses using Kaplan-Meier method included duration of therapy, time to next treatment discontinuation, transformation or death, and overall survival (OS) from the time of cBTKi/BCL2i discontinuation. Results: 339 patients (median age 66 years, interquartile range 59, 73; male 69.6%) met eligibility criteria. Most patients received cBTKi and BCL2i as early lines of therapy: 40.4% received cBTKi in first line and BCL2i in second line; an additional 21.8% received cBTKi in the second line and BCL2i in third line. Transformation was recorded among 24 (7.1%) patients during the study period. Of all eligible patients, 215 had discontinued both cBTKi and BCL2i and could be evaluated for post-cBTKi/BCL2i outcomes. A total of 47 patients (21.9% of the 215 who discontinued therapy) died before receiving subsequent therapy, 116/215 (54%) received subsequent therapy, and the remaining 52/215 (24.2%) were alive without additional treatment after cBTKi/BCL2i exposure. The median time from discontinuation of cBTKi/BCL2i (whichever agent was last) to the immediate next treatment discontinuation, transformation, or death was 4.6 months (95% confidence interaval [CI]: 3.0-6.9). Among those who received subsequent therapy, the most common immediate next line of therapy included additional BCL2i-based therapy (venetoclax re-treatment with or without other agents, n=71/116; 61.2%) or anti-CD20 antibody-based therapy (with or without other agents, 73/116 (62.9%). Fewer patients received PI3K inhibitor-based treatment (n=14/116; 12.1%) or additional cBTKi therapy (n=19/116; 16.4%) at any time after discontinuation of the initial cBTKi/BCL2i. As shown in the Figure, for those who received subsequent therapy (n=116), the median duration of the immediate post-cBTKi/BCL2i therapy was 4.8 months (95% CI: 3.0-7.3). Among the 215 who discontinued cBTKi/BCL2i therapy, median OS from discontinuation was 14.1 months (95% CI: 11.7-21.0). Image:Summary/Conclusion: Patients with CLL/SLL who have been previously treated with both a cBTKi and BCL2i experience poor outcomes as observed by time to next treatment discontinuation, duration of subsequent therapy and overall survival. There remains a need for more effective therapies for patients with CLL/SLL after progression on cBTKi/BCL2i.